1. Field of the Invention
The present invention relates to pharmaceutical compositions in the form of dry powders and methods for making such pharmaceutical compositions. In particular, the present invention is directed to pharmaceutical compositions in the form of fine powders having small size and a narrow size distribution and methods for making such powders.
2. Description of Related Art
There is an increasing desire in the pharmaceutical industry for systems capable of delivering pharmaceuticals to a patient without the use of needles or other devices which are often considered unpleasant or inconvenient by the patient.
One such system that has been utilized is an aerosol delivery system. An aerosol delivery system introduces a predetermined amount of a liquid pharmaceutical into the lungs of a patient in the form of liquid droplets. Such a device is described, for example, in U.S. Pat. No. 4,484,577 by Sackner et al.
It has also been proposed to introduce solid particles of a pharmaceutical composition into the lungs of a patient to deliver the pharmaceutical to the patient's bloodstream. Devices for delivering the powder to the patient's lungs are commonly referred to as dry powder inhalers. Such devices mix a controlled amount of a dry pharmaceutical powder with a gas, usually air, and delivers the dosage to the patient as the patient inhales. Such a device is described, for example, in U.S. Pat. No. 5,492,112 by Mecikalski et al., U.S. Pat. No. 5,351,683 by Chiesi et al. and U.S. Pat. No. 5,320,714 by Brandel, each of which is incorporated herein by reference in its entirety.
Despite the potential advantages of dry powder inhalers, their use has been limited due to a need for improved pharmaceutical powders. Due to the stringent requirement that the dry powder inhaler administer the proper dose of the pharmaceutical, it is generally necessary that the powders have the following properties: high purity; small particle size; narrow particle size distribution; controlled surface chemistry; controlled aerodynamic diameter; and minimal agglomeration. See Broadhead et al., Drug Development and Industrial Pharmacy, 18, 1169 (1992).
The most common method for producing powders of pharmaceutical compositions is referred to as spray-drying. Spray drying of pharmaceutical powders is typically used to form dry powders which can be stored for later use, e.g. later dissolution into a liquid, or for tableting or encapsulation in a pill form. See, for example, U.S. Pat. No. 4,830,858 by Payne et al. The spray drying method is described, for example, in the article "Spray-Drying as a Preparation Method of Microparticulate Drug Delivery Systems: An Overview", Giunchedi et al., STP Pharma Sciences, 5 (4) pgs. 276-290 (1995). However, most spray-drying methods have not been capable of producing particles that are well-suited for dry powder inhalation. Current spray drying techniques typically produce powders having a wide particle size distribution. Further, spray-drying methods have not produced particles having an average particle size which is desirable for dry powder inhaler devices, such as around 2 .mu.m. Therefore, the particles must be mechanically milled, which adversely affects the bioactivity of the particles and the morphology of the particles.
It would therefore be beneficial to provide a pharmaceutical powder batch having an average particle size on the order of 2 .mu.m, a narrow particle size distribution and a low tendency to agglomerate. It would also be advantageous if the particles had a substantially spherical morphology. It would also be advantageous if such powders could be produced in a continuous, high-volume process.